title: Active caspase-3 is stored within secretory compartments of viable mast cells.
abstract: Caspase-3 is a main executioner of apoptotic cell death. The general notion is that, in viable cells, caspase-3 is found as a cytosolic inactive proenzyme and that caspase-3 activation is largely confined to processes associated with cell death. In this study, we challenge this notion by showing that enzymatically active caspase-3 is stored in viable mast cells. The enzymatically active caspase-3 was undetectable in the cytosol of viable cells, but was recovered in subcellular fractions containing secretory granule-localized proteases. Moreover, active caspase-3 was rapidly released into the cytosolic compartment after permeabilization of the secretory granules. Using a cell-permeable substrate for caspase-3, the presence of active caspase-3-like activity in granule-like compartments close to the plasma membrane was demonstrated. Moreover, it was shown that mast cell activation caused release of the caspase-3 to the cell exterior. During the course of mast cell differentiation from bone marrow cells, procaspase-3 was present in cells of all stages of maturation. In contrast, active caspase-3 was undetectable in bone marrow precursor cells, but increased progressively during the process of mast cell maturation, its accumulation coinciding with that of a mast cell-specific secretory granule marker, mouse mast cell protease 6. Together, the current study suggests that active caspase-3 can be stored within secretory compartments of viable mast cells.
authors.affiliation: Department of Anatomy, Uppsala Biomedical Center, Swedish University of Agricultural Sciences, 751 23 Uppsala, Sweden. Gianni.Garcia@slu.se
authors.forename: Gianni
authors.initials: G
authors.lastname: Garcia-Faroldi
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Melo
authors.forename: Elin
authors.initials: E
authors.lastname: Rönnberg
authors.forename: Mirjana
authors.initials: M
authors.lastname: Grujic
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells; D053148:Caspase 3 / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D008407:Mast Cells / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D022142:Secretory Vesicles / Q000201:enzymology* / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D004792:Enzyme Precursors; D033921:Vesicular Transport Proteins; D053148:Caspase 3